1. Field of the Invention
The present disclosure relates to methods for the treatment of abnormal tissues using radionuclide compounds.
2. Description of Related Art
Radiation therapy has been used with some success in treating tumors and other diseases, and can be an effective therapeutic alternative. Radiotherapeutic agents include radionuclides with alpha or energetic beta emissions that can be targeted to disease sites. For example, one therapeutic use of these radiotherapeutic agents is for the locoregional ablation of cancerous cells or tumors. Optimal radiotherapeutic agents deposit sufficient radioactivity in target tissues to kill abnormal or targeted cells while minimizing uptake in nontarget tissues. Therefore, it is generally understood that the effective dose of radiation must be sufficiently limited to the tumor or other target tissue to avoid injuring the surrounding tissues and the overall health of the patient. Currently, only a few radiopharmaceutical particles are available for locoregional treatment of cancerous cells or tumors, such as FDA approved Y-90 particles (Sir-Spheres®) (U.S. Pat. Nos. 6,537,518, 6,258,338 and 5,885,547; Keng et al., (2003) Ann. Acad. Med. Singapore 32(4):518-524; Sarfaraz et al., (2003) Med. Phys. 30(2):199-203).
Directed local treatment of cancer can be achieved by implanting sealed radiation sources into, for example, a post-surgical field for several weeks. Conventional brachytherapy involves the implantation of sealed radiation sources into the post-surgical field for several weeks (Nag et al., (2001) Oncology 15:195-202). Additionally, clinical trials have reported favorable outcomes for treating brain and breast cancer patients using a single implanted catheter filled with Iodine-125 Iotrex and Iridium-192 seeds irradiating the tissues around the post-surgical cavity (Proxima Therapeutices, Inc.) (King et al., (2000) Amer J Surg 180:299-304; Vicini et al., (2002) J Clin Oncol 19:1993). This approach has gained FDA approval, for example GlialSite for brain tumors and MammoSite for breast cancer (deGuzman et al., (2000) J Nucl Med 41 (5 Suppl):274P; Dempsey et al., (1998) Int J Radiat Oncol Biol Phys 42:421-29). Local irradiation of breast cancer using the sealed radioisotope Iridium-192 contained in an inflatable balloon is also an established approach to breast-conservation therapy in patients (Keisch et al., (2003) Int. J. Radiat. Oncol. Biol. Phys. 55(2):289-293; Streeter et al., (2003) Breast 12(6):491-96). This method requires, however, additional surgeries to implant and explant the Iridium-192 device. While these FDA approved approaches illustrate the desirable features of locoregional radionuclide therapy, a more desirable approach would be to directly ablate tumors using, for example, intratumoral injection of readily available radionuclides, without requiring surgical procedures to remove the radiation source(s).
Thus, it is highly desirable to identify a radiopharmaceutical that can be used for locoregional treatment of abnormal tissues, for example a solid tumor or the surrounding tissues after the tumor is removed, which does not require undesirable and tedious steps for synthesizing the radiopharmaceutical, surgical implantation or other more invasive procedures to deliver the radiopharmaceutical to the subject, or invasive procedures to remove the radiation sources(s).